Supplemental oxygen delivery system

ABSTRACT

A supplemental oxygen delivery system is described in which Aerosol is delivered into a housing which sits in the circuit from the supplemental oxygen supply and optional humidifier. The supplemental oxygen passes through this chamber in which the aerosol is located, and collects the aerosol transporting it to a patient via a nasal cannula or a face mask. An aerosol generator is mounted to the housing and delivers aerosol into an oxygen stream flowing between an inlet and an outlet of the housing. The housing also has a removable plug in the base thereof for draining any liquid that accumulates in the housing. There is no disruption of oxygen delivery to patients using nasal cannulas who currently have to use a separate face-mask when receiving nebulized medication.

The present application is a continuation of U.S. patent application No.12/568,399, filed Sep. 28, 2009, the complete contents of which areincorporated herein by reference, and which claims the benefit of U.S.Provisional Application No. 61/100,491, filed Sep. 26, 2008, thecomplete contents of which are Incorporated herein by reference.

INTRODUCTION

The invention relates to a system for delivery of supplemental oxygen toa patient. In particular, the invention relates to a nasal cannulasystem

For patients undergoing mechanical ventilation, aerosol delivery is awell established therapy. Aerosol is added to the humidified inspiratorygas by placing a T-piece or equivalent in the circuit and entraining theaerosol with the humidified inspiratory gas. In such arrangements theaerosolisation device is downstream of the humidifier and upstream ofthe patient.

Continuous flow non-invasive therapy is also known in which a patientcontinues to breathe room air but is supplied with a continuous flow ofsupplemental oxygen delivered via nasal cannula or to a mask via narrowbore tubing. There are two different types of system. The first isgenerally referred to as high flow therapy where the flow requiresadditional heating or humidity to ensure patient comfort. The second issupplemental oxygen therapy where flow rates are low and oxygen isgenerally supplied direct from a wall supply or a gas bottle supply.This latter system is a low cost simplified therapy that does notusually carry the burden of high cost gas conditioning systems such ascontrolled heated humidification equipment.

At present, patients undergoing supplemental oxygen therapy deliveredvia a nasal cannula must be taken off the cannula and must use aseparate facemask or mouthpiece for nebuliser treatment.

STATEMENTS OF INVENTION

According to the invention there is provided a supplemental oxygendelivery system for delivery of supplemental oxygen from an oxygensupply to a patient, the system comprising a delivery tube for deliveryof supplemental oxygen from a supply to a patient; and an aerosolgenerator for delivery of aerosol into the delivery tube.

In one embodiment the system comprises a housing through whichsupplemental oxygen is led, the chamber having an inlet and an outlet.

The housing may be adapted to retain larger aerosol particles within thehousing.

In one embodiment the volumetric mean diameter of particles at theoutlet of the housing is less than the volumetric mean diameter ofparticles generated by the aerosol generator.

The volumetric mean diameter of the aerosol particles at the outlet ofthe housing may be less than 4.5 microns, less than 4 microns, less than3.5 microns, approximately 3 microns.

In one aspect the housing comprises means to encourage localiseddeposition of larger aerosol particles.

The housing may comprise an internal wall to retard the flow of largeraerosol particles. The internal wall may be located between the housinginlet and the housing outlet. In one case the internal wall extendsbelow the level of the housing inlet.

In one embodiment the internal wall comprises a screen to retard theflow or larger particles.

In one case the internal wall defines a baffle.

In one embodiment the housing comprises a screen to retard largeraerosol particles. The screen may be provided by a perforated internaldivider. Alternatively, the screen is provided adjacent to the outletfrom the housing.

In one embodiment the housing inlet is located below the level of thehousing outlet. Alternatively, the housing inlet is locatedsubstantially at the same level as that of the housing outlet.

In one embodiment the housing comprises a chamber for collection ofdroplets.

The housing may comprise a drain port.

In one case the housing comprises a fluid reservoir for humidificationof supplemental oxygen. The housing may comprise means for directingsupplemental oxygen to travel through the fluid reservoir.

In one embodiment the aerosol generator is mounted to the housing fordelivery of aerosol into the housing.

The aerosol generator may comprise an aerosol outlet which is located inthe housing intermediate the housing inlet and the housing outlet.

In one aspect the delivery system comprises a humidifier for humidifyingsupplemental oxygen.

In this case the aerosol generator may be mounted to the humidifier fordelivery of aerosol into humidified supplemental oxygen. The housing maybe located downstream of the humidifier.

In one embodiment the supplemental oxygen delivery tube has a diameterof from 2 mm to 5 mm.

In one embodiment the flow of supplemental oxygen is less than about 3liters per minute.

In one case the delivery system comprises a nasal cannula.

In another case the delivery system comprises a face mask.

The aerosol generator may comprise a vibratable member having aplurality of apertures extending between a first surface and a secondsurface thereof.

The first surface may be adapted to receive fluid to be aerosolised.

The aerosol generator may be configured to generate an aerosol at thesecond surface.

The vibratable member may be dome-shaped in geometry.

In one case the vibratable member comprises a piezoelectric clement.

The system may comprise a controller for controlling the operation ofthe aerosol generator.

The aerosol may contain a therapeutic and/or prophylactic agent.According to the invention there is provided a non-invasive positivepressure ventilation system, especially a nasal cannula systemcomprising an aerosol generator for introducing an aerosol into gaspassing through the non-invasive ventilation system such as a nasalcannula system.

In one embodiment the nasal cannula system comprises a humidifier.

In one case the aerosol generator may be adapted to deliver aerosol intogas passing through the humidifier. The aerosol generator may comprisean outlet through which aerosol is delivered and the outlet is locatedin the humidifier. In one case the humidifier is a bubble humidifier.

In another case the aerosol generator is located downstream of thehumidifier.

In one embodiment the nasal cannula system comprises a housing throughwhich the gas is passed, the aerosol generator comprising an outletthrough which aerosol is delivered and the outlet is located in thehousing. The housing may comprise a gas inlet and a gas outlet and theaerosol generator outlet is located to deliver aerosol into the gas asit passes through the housing.

In one case the housing comprises a chamber for collection of droplets.The chamber may comprise a droplet drainage port.

In one case the aerosol generator itself provides a humidifier.

In one embodiment the aerosol generator comprises a vibratable memberhaving a plurality of apertures extending between a first surface and asecond surface thereof The first surface may be adapted to receive fluidto be aerosolised. The aerosol generator may be configured to generatean aerosol at the second surface.

In one case the vibratable member is dome-shaped in geometry.

The vibratable member may comprise a piezoelectric element.

In one case the apertures in the vibratable member are sized toaerosolise fluid by ejecting droplets of the water such that themajority of the droplets by mass have a size of less than 5 micrometers.

The apertures in the vibratable member may be sized to aerosolise fluidby ejecting droplets of the water such that the majority of the dropletsby mass have a size of less than 3 micrometers.

The system in one case comprises a controller for controlling theoperation of the aerosol generator. The controller may be configured tocontrol the pulse rate at a set frequency of vibration of the vibratablemember. The controller may be impedance matched to the aerosolgenerator.

In one embodiment the system comprises means to determine whether fluidis in contact with the aerosol generator. The determining means may beconfigured to determine at least one electrical characteristic of theaerosol generator. The determining means may be configured to determineat least one electrical characteristic of the aerosol generator over arange of vibration frequencies.

In one case the determining means is configured to compare the at leastone electrical characteristic against a pre-defined set of data.

While the invention is described with reference to a nasal cannulasystem it may be applied to any suitable non-invasive positive pressurebreathing assistance system including a face mask system.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will be more clearly understood from the followingdescription thereof given by way of example only with reference to theaccompanying drawings, in which:

FIG. 1 is a diagram of a nasal cannula system according to an embodimentof the invention;

FIG. 2 is an isometric, partially cut-away view of part of a nasalcannula system according to one embodiment of the invention;

FIGS. 3 to 6 are isometric, partially cut-away views similar to FIG. 2of part of nasal cannula systems according to other embodiments of theinvention;

FIG. 7 is an isometric view of part of another nasal cannula systemaccording to the invention;

FIGS. 8 to 11 are cross sectional views of FIG. 7 illustrating systemparts according to the various embodiments of the invention;

FIG. 12 is an isometric, partially cut-away view of part of anothernasal cannula system according to the invention;

FIGS. 13 to 16 are isometric, partially cut-away views similar to FIG.12 of part of nasal cannula systems according to other embodiments ofthe invention;

FIG. 17 is a diagram of a nasal cannula system according to a furtherembodiment of the invention;

FIG. 18 is an isometric, partially cross sectional view of a nasalcannula system according to another embodiment of the invention;

FIG. 19 is a graph of volume frequency for particle diameters for aknown aerosol system (distribution A) and one aerosol system(distribution B) according to the invention;

FIG. 20 is a schematic illustration of a part of an apparatus accordingto the invention;

FIG. 21 is a schematic illustration of a part of the apparatus;

FIG. 22 is an exploded isometric view of an aerosol generator used inthe invention;

FIG. 23 is a cross-sectional view of the assembled aerosol generator ofFIG. 22;

FIG. 24 is a perspective view of a controller housing used in theapparatus of the invention;

FIGS. 25(a) and 25(b) are graphs of DC voltage versus time and ACvoltage versus time respectively to achieve a 100% aerosol output;

FIGS. 26(a) and 26(b) are graphs of DC voltage versus time and ACvoltage versus time respectively to achieve a 50% aerosol output-FIG.26(a) illustrates the waveform output from a microprocessor to a drivecircuit and FIG. 26(b) illustrates the waveform output from a drivecircuit to a nebuliser;

FIGS. 27(a) and 27(b) are graphs of DC voltage versus time and ACvoltage versus time respectively to achieve a 25% aerosol output-FIG.27(a) illustrates the waveform output from a microprocessor to a drivecircuit and FIG. 27(b) illustrates the waveform output from a drivecircuit to a nebuliser;

FIG. 28 is a graph of AC voltage versus time; and illustrates an outputwaveform from a drive circuit to a nebuliser; and

FIG. 29 is a graph of frequency versus current for another apparatusaccording to the invention.

DETAILED DESCRIPTION

Referring initially to FIG. 1 there is illustrated a cannula systemaccording to the invention in which patient 1 undergoing supplementaloxygen therapy is supplied with gas through narrow bore tubing 2 to anasal cannula 3 or to an oxygen face mask 4. The gas may be suppliedfrom a central supply wall connector 5 or from a bottled source 6.

As the diameter of nasal cannula tubing is generally much smaller thanrespiratory circuits, (2-5 mm ID), it is difficult to transport aerosolalong a length of nasal cannula tubing without considerable losses tocondensate formed as liquid droplets. These liquid droplets can lead topatient discomfort.

This invention provides aerosolization into a chamber 10, which sits inthe circuit from the supplemental oxygen supply or humidifier, if used,but is separate from the humidifier. The supplemental oxygen passesthrough the chamber 10, in which the aerosol generator 9 is located, andcollects the aerosol transporting it to the patient. The chamber 10 isdesigned to selectively allow only smaller aerosol particle sizes (lessthan 3 microns), suitable for transport along narrow bore tubing, ontoto the patient whilst encouraging localised deposition of the aerosolheavier particles.

Various medicaments available in liquid form may be aerosolised for usein therapies. Where the liquid being aerosolised is water, saline orother solution of water or saline, the aerosol generator also providesadditional humidity to the circuit which may enhance patient comfortwhere no other humidity source is present.

Selection of smaller particle sizes may be achieved through use of thefollowing or any combination of the following.

Referring to FIG. 2 in one embodiment of the invention aerosol from anaerosol generator 9 is delivered into a chamber 10, which sits in thecircuit from the supplemental oxygen supply. The supplemental oxygenpasses through this chamber 10, collects the aerosol and transports itto the patient 1 along the small bone tubing 2.

The aerosol generator 9 is mounted to the housing 10 and deliversaerosol 12 into an oxygen stream 13 flowing between an inlet 14 and anoutlet 15 of the housing 10. The housing 10 also has a removable plug 16in the base 17 thereof for draining any liquid that accumulates in thehousing 10. The housing 10 also has support feet 18 so that the housingcan be stood on a suitable surface. The aerosol generator 9 in this casehas an optional adapter 19 for continuous feed, for example from a dripbag. The generator also has a power cable 20 which may connect to anAC/DC adapter or to a control module.

In one case the inlet 14 and outlet 15 are horizontally opposed. Aseparation plane, provided by a depending skirt 25 positioned betweenthe inlet 14 and outlet 15 acts as a baffle to retard particles above acertain size whilst allowing the smaller particles to pass through fortransport along the circuit. The majority of particles that exit thehousing 10 are less than 3 microns. This is achieved through thecombination of impaction on the separation wall 25 and the sharp changein flow direction created by the presence of the wall 25.

Referring to FIG. 3, the separation wall 25 may be extended furthertowards the floor of the chamber to produce a greater impaction surfaceand flow disturbance.

Referring to FIG. 4 the inlet 14 may be positioned at a substantiallylower level (z-direction) relative to the separation plane and theoutlet 15 to further adjust the impaction surface and flow disturbance.

Referring to FIG. 5 in one case a separation wall 26 extends to and isjoined to the floor of the chamber 10 to isolate the aerosol generationspace from the airflow space. The separation wall in this case isporous, mesh or slotted to retard larger particles and allow smallerparticles through to the outlet 15.

Referring to FIG. 6 there may be a screen, mesh or slotted plate 27positioned over the outlet 15 to retard larger particles and allowsmaller particles through to the circuit.

FIGS. 2 to 6 illustrate some features of an aerosol chamber but thedesign is not limited to this profile. Some or all of the elements maybe incorporated into a lower profile design such as the exampleillustrated in FIGS. 7 to 11 in which elements similar to thosedescribed above with reference to FIGS. 2 to 6 are assigned the samereference numerals.

In a separate embodiment, the aerosol can be generated in isolation (forexample in a t-piece fitting), which sits in the circuit from thesupplemental oxygen supply or humidifier, if used, where there is noaerosol particle selection mechanism. Various chambers 30 of this typeare illustrated in FIGS. 12 to 16. The particle separation chamber 30 islocated in the circuit between the aerosol generator and the patient asa stand-alone element and receives a mixture of the therapy gas and thefull spectrum of generated aerosol particle sizes. The chamber 30selectively allows only smaller aerosol particle sizes, suitable fortransport along narrow bore tubing, onto the patient whilst encouraginglocalised deposition of the aerosol heavier particles. The stand-alonechamber 30 may incorporate any combination of the elements describedwith reference to FIGS. 2 to 11.

Patients using a nasal cannula for delivery of oxygen in some cases havethe oxygen passed through a bubble humidifier to humidify the oxygen,preventing drying out of the nasal mucus membranes. Referring to FIG. 17in one embodiment of the invention aerosolisation from an aerosolgenerator 9 may be delivered directly into a bubble humidifier 31 whichis supplied with oxygen from an oxygen supply 5 or 6. The aerosol isentrained with the humidified oxygen as it exits the bubble humidifier31, passing into a cannula 2 to the nasal prongs for delivery to apatient 1.

The invention allows for aerosolization directly into a chamber suitablefor use as a bubble humidifier. This may involve adaptation of existingand commonly available bubble humidifiers to allow addition of theaerosol generator (FIG. 17). This device may be used in combination withan additional downstream baffle box 30 as described with reference toany of FIGS. 12 to 16.

Referring to FIG. 18 a bubble humidifier 35 may incorporate anycombination of the elements outlined above.

Vibrating mesh technology which is described in detail below generatesan aerosol with a precisely controlled particle size range optimised ingeneral respiratory use for deep lung deposition. The distribution ofparticles can be represented as a normal distribution with the majorityof particles produced in the range 2-10 microns. Test data has shownthat the baffle box is effective in removing the larger particles toboth lower the effective mean volumetric diameter and also change thedistribution of particles to only allow those sizes suitable fortransport along narrow bore tubing, onto to the patient with minimalrain-out along the tubing.

EXAMPLE Profile/distribution of Generated Aerosol Before and AfterAction of Baffle Box

Referring to FIG. 19 distribution A represents the normal distributionof aerosol particle diameters as produced by an aerosol generator. Thistest was carried out using a commercially available Aerogen SOLOnebuliser product for general respiratory use. Particle sizes fallbroadly in the range of 1-10 microns. The term “span” is used todescribe the spread of the particle size and is defined as(Dv90-Dv10)/Dv50. Dv90 is the volume diameter below which 90% of allparticle diameters fall, Dv10 is the volume diameter below which 10% ofall particle diameters fall and Dv50 is volume diameter below which 50%of all particle diameters fall.

Typically the Dv50 value is reported as the Volumetric Mean Diameter(VMD). For a specific aerosol generator under test at Aerogen the spanwas recorded as 2.27 and the VMD as 4.85 microns.

Distribution B represents the distribution of aerosol particle diametersproduced by the test aerosol generator as measured after exiting thebaffle box chamber. This testing was carried out using a commerciallyavailable Aerogen SOLO nebuliser product fitted to a chamber configuredwith lower inlet position, flow diversion and a screen as represented inFIGS. 4 & 6. Larger particles are removed from the distribution and onlyparticles suitable for transport along narrow bore tubing are passedthrough the baffle box. For the specific aerosol generator under testthe span was reduced to 0.76 and the VMD was reduced to 3 microns.

In the invention aerosol is delivered through single narrow bore tubingat flow rates up to 3 1 pm, such that rainout is minimized and drugdeposition is maximised at the delivery point of a face mask or a nasalcannula.

The invention has the following advantages:—

-   -   Drug delivery via nasal cannula is not currently performed    -   For convenience, patients may have medication delivered via the        nasal cannula or narrow bore tubing to a face mask without the        use of a separate nebulizer combined with a mouthpiece or mask.    -   No disruption to the oxygen delivery to patients using nasal        cannulas who have to use a separate face-mask when receiving        nebulized medication.    -   Improve patient comfort by reducing occurrence of liquid        droplets entering the nasal passage through selectively sorting        particle sizes better suited to transportation along narrow-bore        tubing.    -   Vibrating mesh aerosol generator does not require any gas flow        to create aerosol. Can be used with very low in circuit gas        flows.    -   Designed to work with standard off-the-shelf cannulas with        single bore tubing without need for re-circulation systems.    -   Prevent condensate from forming in tubing through selection of        aerosol particle sizes rather than gathering condensate in a        trap near to the patient.    -   Simple system without cost and complexity of heated        humidification, drug delivery and re-circulation.    -   Aerosol vibrating mesh technology maintains separation of        medication reservoir from circuit to avoid contamination. There        is no recirculation circuit required.    -   Aerosol vibrating mesh technology has zero residual drug volume        in the reservoir. This ensures precise control of delivered dose        and good control of delivery for small doses. (expensive drugs).    -   Vibrating mesh technology generates an aerosol with a precisely        controlled particle size range optimised in general respiratory        use for deep lung deposition.

The invention may be used in emergency wards for patients undergoingoxygen treatment via nasal cannula and respite care of same inmechanical ventilation.

In one aspect of the invention, an aerosol generator 9 is used todeliver an aerosolised humidifying agent into the gas. The humidifyingagent may be sterile water or sterile saline with a salt concentrationin the range from 1 micromolar to 154 millimolar. Such salineconcentrations can be readily nebulised using the aerosolisationtechnology used in the invention.

Any suitable medicament, therapeutic agent, active substance orpharmaceutically active compound than can be nebulised may be employed.It can also act to deliver any agent presented in an aqueous drugsolution.

The system facilitates delivery in aerosol form of, for example,bronchodilators, including β-agonists, muscarinic antagonists,epinephrine;, surfactants; pain-relief medications includinganaesthetics; migraine therapies; anti-infectives; anti-inflammatories,steroids, including corticostroids; chemotherapeutic agents; mucolytics;vasodilators; vaccines and hormones. In addition substances classifiedas anti-thrombogenic agents, anti-proliferative agents, monoclonalantibodies, anti-neoplastic agents, anti-mitotic agents, anti-senseagents, anti-microbial agents, nitric oxide donors, anti-coagulants,growth factors, translational promoter, inhibitors of heat shockproteins, biomoloecules including proteins, polypeptides and proteins,oligonucleotides, oligoproteins, siRNA, anti-sense DNA and RNA,ribozymes, genes, viral vectors, plasmids, liposomes, angiogenicfactors, hormones, nucleotides, amino acids, sugars, lipids, serineproteases, anti-adhesion agents including but not limited to hyaluronicacid, biodegradable barrier agents may also be suitable.

The medicament may for example, comprise long-acting beta-adrenoceptoragonists such as salmeterol and formoterol or short-actingbeta-adrenoceptor agonists such as albuterol.

The medicament may be a long-acting muscarinic antagonists such astiotropium (Spiriva) or short-acting muscarinic antagonists such asipratropium (Atrovent).

Typical anti-infectives include antibiotics such as an aminoglycoside, atetracycline, a fluroquinolone; anti-microbials such as a cephalosporin;and anti-fungals. Examples of antibiotics include anti-gram-positiveagents such as macrolides, e.g. erythromycin, clarithromycin,azithromycin, and glycopeptides, e.g. vancomycin and teicoplanin, aswell as any other anti-gram-positive agent capable of being dissolved orsuspended and employed as a suitable aerosol, e.g. oxazoldinone,quinupristin/dalfopristen, etc. Antibiotics useful as anti-gram-negativeagents may include aminoglycosides, e.g. gentamicin, tobramycin,amikacin, streptomycin, netilmicin, quinolones, e.g. ciprofloxacin,ofloxacin, levofloxacin, tetracyclines, e.g. oxytetracycline,dioxycycline, minocycline, and cotrimoxazole, as well as any otheranti-gram-negative agents capable of being dissolved or suspended andemployed as a suitable aerosol.

Anti-inflammatories may be of the steroidal such as budesonide orciclesonide, non-steroidal, such as sodium cromoglycate or biologicaltype.

Typical local anaesthetics are, for example, Ropivacaine, Bupivacaine,levobupivacaine, and Lidocaine.

Chemotherapeutic agents may be alkylating agents, antimetabolites,anthracyclines, plant alkaloids, topoisomerase inhibitors, nitrosoureas,mitotic inhibitors, monoclonal antibodies, tyrosine kinase inhibitors,hormone therapies including corticosteroids, cancer vaccines,anti-estrogens, aromatase inhibitors, anti-androgens, anti-angiogenicagents and other anti-tumour agents.

Surfactant medications (sometimes referred to herein as “surfactants”)are protein-lipid compositions, e.g. phospholipids, that are producednaturally in the body and are essential to the lungs' ability to absorboxygen. They facilitate respiration by continually modifying surfacetension of the fluid normally present within the air sacs, or alveoli,that tube the inside of the lungs. In the absence of sufficientsurfactant, these air sacs tend to collapse, and, as a result, the lungsdo not absorb sufficient oxygen. Insufficient surfactant in the lungsresults in a variety of respiratory illnesses in both animals andhumans. Since most of these surfactant medications are animal-based, thecurrent supply is limited, and although synthetic surfactants areavailable, their manufacture is both inexact and expensive. In addition,the surfactant medications are typically high in viscosity and aredifficult to deliver to the patient's respiratory system. The increasedefficiency of the pressure-assisted breathing system of the presentinvention, and the smaller amount of medicament required for a treatmentaccording to the present invention, can be a substantial advantage whensuch scarce and expensive medicaments are employed. The combination ofsurfactant with other medicaments to improve distribution in the lungand body is also possible. Surfactants also possess the capacity to actas anti-adhesion agents.

In the invention an aerosol is delivered into the nasal cannula circuit.The distinction between aerosol and vapour is in the size of theparticles. The majority of aerosol particles that the aerosol generatorproduces are in the 0.5 to 5.0 micron diameter range. Water vapour onthe other hand contains individual water molecules which areapproximately 0.00001 microns i.e. 10,000 times smaller than the aerosolparticles.

Referring to FIGS. 20 to 29, the apparatus comprises a reservoir 100 forstoring sterile water or saline solution which may or may not contain adrug, the aerosol generator 9 for aerosolising the solution, and acontroller 103 for controlling the operation of the aerosol generator 9.

This aerosol generator 9 converts the water into an aerosol of a verydefinable particle size. The volumetric median diameter (VMD) wouldtypically be in the range of 2-10 microns.

The controller 103 is used to provide electrical power to drive theaerosol generator 9. This provides the aerosolising action to conveyaerosol to the supplemental oxygen being delivered to a patient.

The nebuliser (or aerosol generator) 9, has a vibratable member which isvibrated at ultrasonic frequencies to produce liquid droplets. Somespecific, non-limiting examples of technologies for producing fineliquid droplets is by supplying liquid to an aperture plate having aplurality of tapered apertures extending between a first surface and asecond surface thereof and vibrating the aperture plate to eject liquiddroplets through the apertures. Such technologies are describedgenerally in U.S. Pat. Nos. 5,164,740; 5,938,117; 5,586,550; 5,758,637;-6755189, 6540154, 6926208, 7174888, 6546927, 6,085,740, andUS2005/021766A, the complete disclosures of which are incorporatedherein by reference. However, it should be appreciated that the presentinvention is not limited for use only with such devices.

In use, the liquid to be aerosolised is received at the first surface,and the aerosol generator 9 generates the aerosolised liquid at thesecond surface by ejecting droplets of the liquid upon vibration of thevibratable member. The apertures in the vibratable member are sized toaerosolise the liquid by ejecting droplets of the liquid such that themajority of the droplets by mass have a size of less than 5 micrometers.

Referring particularly to FIGS. 22 and 23, in one case the aerosolgenerator 9 comprises a vibratable member 140, a piezoelectric element141 and a washer 142, which are sealed within a silicone overmould 143and secured in place within a housing 136 using a retaining ring 144.The vibratable member 140 has a plurality of tapered apertures extendingbetween a first surface and a second surface thereof.

The first surface of the vibratable member 140, which in use facesupwardly, receives the liquid from the reservoir 101 and the aerosolisedliquid, is generated at the second surface of the vibratable member 140by ejecting droplets of liquid upon vibration of the member 140. In usethe second surface faces downwardly. In one case, the apertures in thevibratable member 140 may be sized to produce an aerosol in which themajority of the droplets by weight have a size of less than 5micrometers.

The vibratable member 140 could be non-planar, and may be dome-shaped ingeometry.

The complete nebuliser may be supplied in sterile form, which is asignificant advantage. The aerosol generator unit may comprise a collaror neck 136 to facilitate mounting of the unit, for example to thehousings 20, 30. The interfitting may be a push fit. This enables theunit to be easily mounted and de-mounted, for example for cleaning. Theneck or collar 136 at least partially lines the opening into the housing20, 30 and may project inwardly to define an internal wall as describedabove.

Referring particularly to FIG. 20, the controller 103 controls operationof and provides a power supply to the aerosol generator 9. The aerosolgenerator 9 has a housing which defines the reservoir 101. The housinghas a signal interface port 138 fixed to the lower portion of thereservoir 101 to receive a control signal from the controller 103. Thecontroller 103 may be connected to the signal interface port 138 bymeans of a control lead 139 which has a docking member 150 for matingwith the port 138. A control signal and power may be passed from thecontroller 103 through the lead 139 and the port 138 to the aerosolgenerator 9 to control the operation of the aerosol generator 9 and tosupply power to the aerosol generator 9 respectively.

The power source for the controller 103 may be an on-board power source,such as a rechargeable battery, or a remote power source, such as amains power source, or an insufflator power source. When the remotepower source is an AC mains power source, an AC-DC converter may beconnected between the AC power source and the controller 103. A powerconnection lead may be provided to connect a power socket of thecontroller 103 with the remote power source.

Referring particularly to FIG. 24 the controller 103 has a housing and auser interface to selectively control operation of the aerosol generator9. Preferably the user interface is provided on the housing which, inuse, is located remote from the aerosol generator housing. The userinterface may be in the form of, for example, an on-off button. In oneembodiment a button can be used to select pre-set values for simplicityof use. In another embodiment a dial mechanism can be used to selectfrom a range of values from 0-100%. This embodiment has the advantage ofproviding the aerosol at a much lower flow rate which will ‘rain out’less and alleviate the need for the baffle box system.

Status indication means are also provided on the housing to indicate theoperational state of the aerosol generator 9. For example, the statusindication means may be in the form of two visible LED's, with one LEDbeing used to indicate power and the other LED being used to indicateaerosol delivery. Alternatively one LED may be used to indicate anoperational state of the aerosol generator 9, and the other LED may beused to indicate a rest state of the aerosol generator 9.

A fault indicator may also be provided in the form of an LED on thehousing. A battery charge indicator in the form of an LED may beprovided at the side of the housing.

The liquid in the reservoir 101 flows by gravitational action towardsthe aerosol generator 9 at the lower medicament outlet. The controller103 may then be activated to supply power and a control signal to theaerosol generator 9, which causes the piezoelectric element 141 tovibrate the non-planar member 140. This vibration of the non-planarmember 140, causes the aqueous solution at the top surface of the member140 to pass through the apertures to the lower surface where the aqueoussolution is aerosolised by the ejection of small droplets of solution.

A flow rate sensor/meter may be used to determine the flow rate of theventilation gas. In response to the fluid flow rate of the ventilationgas, the controller 103 commences operation of the aerosol generator 9to aerosolise the aqueous solution. The aerosolised aqueous solution isentrained with the ventilation gas, and delivered to the patient.

In the event of alteration of the fluid flow rate of the ventilationgas, the flow rate sensor/meter determines the alteration, and thecontroller 103 alters the pulse rate of the vibratable member of thenebuliser accordingly.

The controller 103 is in communication with the flow rate sensor/meter.The controller 103 is configured to control operation of the aerosolgenerator 9, responsive to the fluid flow rate of the ventilation gasand also independent of the fluid flow rate of the ventilation gas asrequired.

In one case, the controller 103 is configured to control operation ofthe aerosol generator 9 by controlling the pulse rate at a set frequencyof vibration of the vibratable member, and thus controlling the fluidflow rate of the aqueous solutions. This has the advantage of reducing‘rain out’ such as by way of reduced aerosol velocity.

The controller 103 may comprise a microprocessor 104, a boost circuit105, and a drive circuit 106. FIG. 20 illustrates the microprocessor104, the boost circuit 105, the drive circuit 106 comprising impedancematching components (inductor), the nebuliser 9, and the aerosol. Theinductor impedance is matched to the impedance of the piezoelectricelement of the aerosol generator 9. The microprocessor 104 generates asquare waveform of 128 KHz which is sent to the drive circuit 106. Theboost circuit 105 generates a 12V DC voltage required by the drivecircuit 106 from an input of either a 4.5V battery or a 9V AC/DCadapter. The circuit is matched to the impedance of the piezo ceramicelement to ensure enhanced energy transfer. A drive frequency of 128 KHzis generated to drive the nebuliser at close to its resonant frequencyso that enough amplitude is generated to break off droplets and producethe aerosol. If this frequency is chopped at a lower frequency such thataerosol is generated for a short time and then stopped for a short timethis gives good control of the nebuliser's flow rate. This lowerfrequency is called the pulse rate.

The drive frequency may be started and stopped as required using themicroprocessor 4. This allows for control of flow rate by driving thenebuliser 9 for any required pulse rate. The microprocessor 104 maycontrol the on and off times to an accuracy of milliseconds.

The nebuliser 9 may be calibrated at a certain pulse rate by measuringhow long it takes to deliver a know quantity of solution. There is alinear relationship between the pulse rate and the nebuliser flow rate.This may allow for accurate control over the delivery rate of theaqueous solution.

The nebuliser drive circuit consists of the electronic componentsdesigned to generate output sine waveform of approximately 100V AC whichis fed to nebuliser 9 causing aerosol to be generated. The nebuliserdrive circuit 106 uses inputs from microprocessor 104 and boost circuit105 to achieve its output. The circuit is matched to the impedance ofthe piezo ceramic element to ensure good energy transfer.

The aerosol generator 9 may be configured to operate in a variety ofdifferent modes, such as continuous, and/or phasic, and/or optimised.

The pulse control is particularly relevant in the case where the aerosolgenerator itself provides a humidifier.

For example, referring to FIG. 25(a) illustrates a 5V DC square waveformoutput from the microprocessor 104 to the drive circuit 106. FIG. 25(b)shows a low power, ˜100V AC sine waveform output from drive circuit 106to nebuliser 9. Both waveforms have a period p of 7.8 μS giving them afrequency of 1/7.8 μs which is approximately 128 KHz. Both waveforms arecontinuous without any pulsing. The aerosol generator may be operated inthis mode to achieve 100% aerosol output.

Referring to FIGS. 26(a) in another example, there is illustrated a 5VDC square waveform output from the microprocessor 104 to the drivecircuit 106. FIG. 26(b) shows a low power, ˜100V AC sine waveform outputfrom the drive circuit 6 to the nebuliser 9. Both waveforms have aperiod p of 7.8 μS giving them a frequency of 1/7.8 μs which isapproximately 128 KHz. In both cases the waveforms are chopped(stopped/OFF) for a period of time x. In this case the off time x isequal to the on time x. The aerosol generator may be operated in thismode to achieve 50% aerosol output.

In another case, referring to FIGS. 27(a) there is illustrated a 5V DCsquare waveform output from microprocessor 104 to drive circuit 106.FIG. 27(b) shows a low power, ˜100V AC sine waveform output from thedrive circuit 106 to the nebuliser 9. Both waveforms have a period p of7.8 μS giving them a frequency of 1/7.8 μs which is approximately 128KHz. In both cases the wavefoms are chopped (stopped/OFF) for a periodof time x. In this case the off time is 3x while the on time is x. Theaerosol generator may be operated in this mode to achieve 25% aerosoloutput.

Referring to FIG. 28, in one application pulsing is achieved byspecifying an on-time and off-time for the vibration of the apertureplate. If the on-time is set to 200 vibrations and off-time is set to200 vibrations, the pulse rate is 50% (½ on ½ off). This means that theflow rate is half of that of a fully driven aperture plate. Any numberof vibrations can be specified but to achieve a linear relationshipbetween flow rate and pulse rate a minimum number of on-time vibrationsis specified since it takes a finite amount of time for the apertureplate to reach its maximum amplitude of vibrations.

The drive frequency can be started and stopped as required by themicroprocessor; this allows control of flow rate by driving thenebuliser for any required pulse rate. The microprocessor can controlthe on and off times with an accuracy of microseconds.

A nebuliser can be calibrated at a certain pulse rate by measuring howlong it takes to deliver a known quantity of solution. There is a linearrelationship between the pulse rate and that nebuliser's flow rate. Thisallows accurate control of the rate of delivery of the aerosolisedaqueous solution.

The pulse rate may be lowered so that the velocity of the emergingaerosol is much reduced so that impaction rain-out is reduced.

Another embodiment may have a reduced hole size on the aperture platewhich will generate an aerosol with a reduced particle size (<3 um) andat a slower flow rate to provide less ‘rain out’ in the tubing system.

Detection of when the aperture plate is dry can be achieved by using thefact that a dry aperture plate has a well defined resonant frequency. Ifthe drive frequency is swept from 120 kHz to 145 kHz and the current ismeasured then if a minimum current is detected less than a set value,the aperture plate must have gone dry. A wet aperture plate hasdiminished or no resonant frequency. The apparatus of the invention maybe configured to determine whether there is any of the first fluid incontact with the aerosol generator 9. By determining an electricalcharacteristic of the aerosol generator 9, for example the currentflowing through the aerosol generator 9, over a range of vibrationfrequencies, and comparing this electrical characteristic against apre-defined set of data, it is possible to determine whether the aerosolgenerator 9 has any solution in contact with the aerosol generator 9.FIG. 29 illustrates a curve 80 of frequency versus current when there issome of the solution in contact with the aerosol generator 9, andillustrates a curve 90 of frequency versus current when there is none ofthe solution in contact with the aerosol generator 2. FIG. 29illustrates the wet aperture plate curve 80 and the dry aperture platecurve 90.

If an application requires a constant feed from a drip bag then a pumpcan be added in line to give fine control of the liquid delivery ratewhich can be nebulised drip by drip. The rate would be set so thatliquid would not build up in the nebuliser. This system is particularlysuitable for constant low dose delivery.

The invention is not limited to the embodiments hereinbefore describedwhich may be varied in detail.

The invention claimed is:
 1. A fluid delivery system for delivery offluid from a fluid supply to a patient, the system comprising: anaerosol generator including a vibratable member having a plurality ofapertures extending between a first surface and a second surfacethereof; a chamber coupled to the aerosol generator; a cylindrical wallextending into the chamber and aligned with a longitudinal axis of theaerosol generator, a fluid supply fluidly coupled to the chamber at aninlet port, the inlet port having a central longitudinal axis that isnormal to the cylindrical wall and intersects the cylindrical wall; anda nasal port fluidly coupled to the chamber.
 2. The system of claim 1,wherein the fluid is supplemental oxygen.
 3. The system of claim 2,wherein a flow rate of the supplemental oxygen is less than about 3liters per minute.
 4. The system of claim 1, wherein the first surfaceis configured to receive fluid to be aerosolised.
 5. The system of claim1, wherein the aerosol generator is configured to generate aerosolparticles adjacent the second surface.
 6. The system of claim 1, whereinthe vibratable member is dome-shaped.
 7. The system of claim 1, whereinthe vibratable member includes a piezoelectric element.
 8. The system ofclaim 1, wherein the nasal port includes a nasal cannula.
 9. A fluiddelivery system for delivery of fluid from a fluid supply to a patient,the system comprising: an aerosol generator including a vibratablemember having a plurality of apertures extending between a first surfaceand a second surface thereof; a chamber coupled to the aerosolgenerator; a cylindrical wall extending into the chamber and alignedwith a longitudinal axis of the aerosol generator and having a distalopening in the chamber, a fluid supply fluidly coupled to the chamber atan inlet port, the inlet port having a central longitudinal axis thatextends into the cylindrical wall, the central longitudinal axisintersecting the longitudinal axis of the aerosol generator between theaerosol generator and the distal opening of the cylindrical wall; and anasal port fluidly coupled to the chamber.
 10. The system of claim 9,wherein the fluid is supplemental oxygen.
 11. The system of claim 10,wherein the vibratable member includes a piezoelectric element.
 12. Thesystem of claim 10, wherein the nasal port includes a nasal cannula. 13.The system of claim 10, wherein the aerosol generator is configured togenerate aerosol particles, and wherein the aerosol particles contain atherapeutic and/or prophylactic agent.
 14. A fluid delivery system fordelivery of fluid from a fluid supply to a patient, the systemcomprising: an aerosol generator; a chamber coupled to the aerosolgenerator; a cylindrical wall protruding into the chamber and alignedwith a longitudinal axis of the aerosol generator, an aerosol generatorreservoir and interface port located opposite the cylindrical wall, theaerosol generator reservoir extending along a central longitudinal axisangled with respect to the longitudinal axis of the aerosol generator; afluid supply fluidly coupled to the chamber at an inlet port that isnormal to the cylindrical wall; and a nasal port fluidly coupled to thechamber.
 15. The system of claim 14, wherein the fluid is supplementaloxygen.
 16. The system of claim 14, wherein the nasal port includes anasal cannula.
 17. The system of claim 14, wherein the aerosol generatorincludes a vibratable member having a plurality of apertures extendingbetween a first surface and a second surface thereof.
 18. The system ofclaim 17, wherein the vibratable member includes a piezoelectricelement.